Diagnosing and staging epithelial ovarian cancer by serum glycoproteomic profiling.

Background There is a need for diagnostic tests for screening, triaging and staging of epithelial ovarian cancer (EOC). Glycoproteomics of blood samples has shown promise for biomarker discovery.

We applied glycoproteomics to serum of people with EOC or benign pelvic masses and healthy controls. A total of 653 analytes were quantified and assessed in multivariable models, which were tested in an independent cohort. Additionally, we analyzed glycosylation patterns in serum markers and in tissues.

We identified a biomarker panel that distinguished benign lesions from EOC with sensitivity and specificity of 83.5% and 90.1% in the training set, and of 86.7 and 86.7% in the test set, respectively. ROC analysis demonstrated strong performance across a range of cutoffs. Fucosylated multi-antennary glycopeptide markers were higher in late-stage than in early-stage EOC. A comparable pattern was found in late-stage EOC tissues.

Blood glycopeptide biomarkers have the potential to distinguish benign from malignant pelvic masses, and early- from late-stage EOC. Glycosylation of circulating and tumor tissue proteins may be related. This study supports the hypothesis that blood glycoproteomic profiling can be used for EOC diagnosis and staging and it warrants further clinical evaluation. This is a preview of subscription content, access via your institution Access options Similar content being viewed by others Data availability Glycoproteomic data are available at ftp://massive.ucsd.edu/v07/MSV000094219/

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We thank all the colleagues at InterVenn Biosciences, in particular Ranjan Bhadra for sample management, Cassie Xu for establishing protocols to analyze mRNA sequencing data, and Hector Huang, Robert Cheng, Itati Hundal and Gregg Czerwieniec for support with mass spectrometry analysis. We are grateful to Carlito Lebrilla for reviewing the manuscript and providing feedback. Funding This study was funded by InterVenn Bioscience. FJ was supported by the Swiss Cancer Research foundation (project number KFS-5389-08-2021-R). Author information Authors and Affiliations Contributions Project conceptualization: CD, DS, KL, FS. Data generation and analysis: CD, PR, GX, CP, TC, MW, RR, BZ, AS, PA, CC, FJ. Data visualization: CD, PR, CP, BZ, PA, FJ. Clinical samples acquisition: KM. Manuscript writing: CD, KL, FS. Manuscript review, editing and approval: all authors. Corresponding author Ethics declarations Competing interests CD, PR, GX, CP, TC, MW, RR, BZ, AS, PA, CWC, KM, DS, KS and FS are or were employees of InterVenn, a company that discovers biomarkers and develops diagnostic tests. TJH received consulting fees from AZ, Caris, Clovis, Eisai, Epsilogen, Genelux, Genentech, GSK, Immunogen, J&J, Merck, Mersana, and Seagen. TJH also received support for attending meetings and/or travel from Alkermes and is on the leadership board of the GOG foundation. Additionally, TJH participated in a Data Safety Monitoring Board/Advisory Board with Corcept. ABO attended advisory board meetings for Merck, GSK, AZ, Genentech, Immunogen. Ethics approval and consent to participate All subjects gave written informed consent to participate. The study was approved by an institutional review board (WCG IRB 20223899 and WIRB IRB 20190246) and performed in accordance with the Declaration of Helsinki. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary information Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Dhar, C., Ramachandran, P., Xu, G. et al. Diagnosing and staging epithelial ovarian cancer by serum glycoproteomic profiling. Br J Cancer 130, 1716–1724 (2024). https://doi.org/10.1038/s41416-024-02644-4 Received: Revised: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1038/s41416-024-02644-4